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Nature 227:518–520 Panda S, Nayak SK, Campo B, Walker JR, Hogenesch JB, Jegla T (2005) Illumination of the melanopsin signaling pathway. Science 307:600–604 Patterson RL, van Rossum DB, Gill DL (1999) Store operated Ca2+ entry: evidence for a secretionlike coupling model. Cell 98:487–499 Peng JB, Chen XZ, Berger UV, Vassilev PM, Tsukaguchi H, Brown EM, Hediger MA (1999) Molecular cloning and characterization of a channel-like transporter mediating intestinal calcium absorption. J Biol Chem 274:22739–22746 Perez CA, Huang L, Rong M, Kozak, JA, Preuss AK, Zhang H, Max M, Margolskee RF (2002) A transient receptor potential channel expressed in taste receptor cells.

Perhaps oligomerization of two or more receptors acts to hide exposed hydrophobic surfaces that would otherwise signal an improperly folded receptor and would be recognized as such by the quality control apparatus of the cell. While the exact purpose of endoplasmic reticulum oligomerization is not currently known, one theory is that it plays a regulatory role in post-translational control of cell surface expression of these, and possibly other, proteins. Pharmacological Chaperone Rescue of the GnRHR While perturbations of single residues in the GnRH receptors from HH patients lead to reduced cell surface expression of the proteins, other modifications to the amino acid sequence have been found to increase the surface expression of the GnRH receptor molecules.

2004). Significantly, it appears as though most of the mutant proteins were fully capable of binding to ligand and transducing a signal, but the receptors were simply misrouted within the cell and so were not accessible to ligand. The receptors that were rescued to the plasma membrane appeared to function identically to the wild type receptor, with the same rank order of potency for ligands, the same affinity for agonist and the same turnover rates (Janovick et al. 2002). The only difference that could be observed was that there was little or no plasma membrane expression in the absence of pharmacoperone.

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